Human Platelet Lysate Supports Efficient Expansion and Stability of Wharton’s Jelly Mesenchymal Stromal Cells via Active Uptake and Release of Soluble Regenerative Factors

Abstract

Manufacturing of mesenchymal stromal cell (MSC)-based therapies for regenerative medicine requires the use of suitable supply of growth factors that enhance proliferation, cell stability and potency during cell expansion. Human blood derivatives such as human platelet lysate (hPL) have emerged as a feasible alternative for cell growth supplement. Nevertheless, composition and functional characterization of hPL in the context of cell manufacturing is still under investigation, particularly regarding the content and function of pro-survival and pro-regenerative factors. We performed comparative analyses of hPL, human serum (hS) and fetal bovine serum (FBS) stability and potency to support Wharton’s jelly (WJ) MSC production. We demonstrated that hPL displayed low inter-batch variation and unique secretome profile that was not present in hS and FBS. Importantly, hPL-derived factors including PDGF family, EGF, TGF-alpha, angiogenin and RANTES were actively taken up by WJ-MSC to support efficient expansion. Moreover, hPL but not hS or FBS induced secretion of osteoprotegerin, HGF, IL-6 and GRO-alpha by WJ-MSC during the expansion phase. Thus, hPL is a suitable source of factors supporting viability, stability and potency of WJ-MSC and therefore constitutes an essential raw material that in combination with WJ-MSC introduces a great opportunity for the generation of potent regenerative medicine products.

Brief communication: Effects of conditioned media from human platelet lysate cultured MSC on osteogenic cell differentiation in vitro

“…In previous studies, we have shown that CM from FBS-cultured BMSC contains several growth factors and cytokines with antiapoptotic and antioxidant properties, including platelet-derived growth factor (PDGF) and vascular endothelial growth factor A (VEGFA), and enhances in vitro osteogenic differentiation of MSC ( Al-Sharabi et al, 2014 ; Al-Sharabi et al, 2016 ; Saleem et al, 2021 ). In context, HPL also contains several growth factors and cytokines, including PDGF, epidermal growth factor (EGF), insulin-like growth factor (IGF), transforming growth factor (TGF), FGF2, stem cell-growth factor-beta (SCGF), interleukin (IL)-1β, IL-2, -6, -10, -12p70, and IL-17A, tumor necrosis factor (TNF)-α and interferon (IFN) ( Cañas-Arboleda et al, 2020 ; Shanbhag et al, 2020a ). Therefore, it is reasonable to postulate that CM of HPL-cultured MSC would be correspondingly more enriched.…”

Combination of human platelet lysate and 3D gelatin scaffolds to enhance osteogenic differentiation of human amniotic fluid derived mesenchymal stem cells

“…This indicates that it can be a useful biological material for stem cell engineering and regenerative medicine [ 76 ]. Similarly, Caas-Arboleda et al verified that hPL is an appropriate supply of factors that support the survivability, stability, and potency of WJ-MSC, offering significant possibilities for the development of effective regenerative medicine [ 77 ].…”

Early detection of optic nerve head changes using optical coherence tomography after using mesenchymal stromal cells as intravitreal therapy in rabbit models of ocular hypertension

“…[ 15 ] and Cañas-Arboleda et al . [ 16 ]. Umbilical cord fragments were washed in 0.9% saline solution with 10,000 U/mL 1% penicillin/streptomycin, and umbilical veins, arteries, and outer membranes were removed.…”